The overall goal of this project is to study intermediates in the biochemical pathway that produce melanoma and to study drugs affecting the release of pituitary-releasing factors with the ultimate hope of applying this information to the control of melanoma. The approaches to be used include biochemical manipulations of murine and human melanomas being grown in long-term tissue culture and in vivo studies of mice containing these transplanted tumor cells. The experiments performed include the addition of melanin precursors to tissue culture cell lines and assaying their effects on [3H]TdR and [14C]leucine incorporation. These drugs include L-dopa, dopamine, and dopamethylester. In addition, antidopamine drugs such as Pimozide, Domperidone, and Spiroperidol are being investigated in a similar fashion. Internal controls include counting of cell numbers and assessing cell viability by using trypan blue exclusion criteria. Transplantation of human melanomas into nude mice with administration of drugs found effective in vitro is also being performed. These results are correlated with the presence or absence of specific membrane-bound receptors to dopamine, which are determined by a competitive binding assay. These studies may provide a rationale for the investigation of drugs affecting the neuroendocrine system in patients with melanoma. (B)